Storage of codes in molecularly imprinted polymers

ABSTRACT

Disclosed is a molecularly imprinted polymer for storing a defined value of a numerical code, more particularly a binary code, in the molecular imprints of said polymer, and a method for the production of said polymer. The molecular imprinting process uses suitable templates comprising a defined sequence of at least two different structural units, each having a different chemical functionality.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a national phase application of PCT Application No.PCT/AT2017/060111, filed Apr. 27, 2017, entitled “STORAGE OF CODES INMOLECULARLY IMPRINTED POLYMERS”, which claims priority to AT20160050393,dated Apr. 29, 2016, and which is incorporated by reference in itsentirety.

BACKGROUND 1) Field of the Invention

The invention relates to the storage of numerical codes, moreparticularly binary codes, in a polymer structure based on a molecularlyimprinted polymer that is provided with complementary imprints of asequence of at least two different chemical functionalities of atemplate.

2) Description of Related Art

The ability to store digital information on conventional hard drives andsimilar data carriers will reach its limit in the near future, becausethe storage densities of such carriers cannot be extended as required.Exponential growth in data volumes requires the development ofadditional, alternative storage methods or materials. Binary-encodedmacromolecules represent here an opportunity for long-term preservationof digital data.

The model for data storage in polymers can be found in natural DNA.Sequences of nucleobases, linked to a phosphate- and sugarmolecular-based polymer backbone, carry a large volume of informationthat can be translated into protein molecules. Such DNA sequences mayalso be produced synthetically. Specific sequencing of the nucleobasesused makes it possible to represent and store digitalized data such astext, images, and audio in binary code (“Towards practical,high-capacity, low-maintenance information storage in synthesized DNA.”Nature, 494: 77-80, 2013; “Robust Chemical Preservation of DigitalInformation on DNA in Silica with Error-Correcting Codes.” Angew. Chem.Int. Ed., 54: 2552-2555, 2015).

Non-natural polymers such as poly(alkoxyamine amide)s can also be used,however, to store digital information (“Design and synthesis ofdigitally encoded polymers that can be decoded and erased.” Nat. Commun.6: 7237, 2015).

In the face of DNA, and with non-natural polymers, the data or codes arethus synthesized directly, wherein the synthesized polymer itself actsas the data storage.

Also known from the prior art is the principle of molecular imprintingof polymers (molecularly imprinted molecules (MIPs)). Molecularimprinting is a technique developed, inter alia, by the Mosbach group;see “Drug assay using antibody mimics made by molecular imprinting.”Nature 361: 645-647, 1993; “Molecularly Imprinted Polymers and Their Usein Biomimetic Sensors.” Chem. Rev. 100 (7): 2495-2504, 2000; “MolecularImprinting: Synthetic Materials as Substitutes for Biological Antibodiesand Receptors. Chem. Mater.” 20 (3): 859-868, 2008; “Synthesis ofsubstrate-selective polymers by hostguest polymerization.” Makromol.Chem. 182 (2): 687-692, 1981; “New Configurations and Applications ofMolecularly Imprinted Polymers” J. Chromatogr. A, 889: 15-24, 2000;Brüggemann O (2002) “Molecularly imprinted materials—receptors moredurable than nature can provide.” Chapter in Advances in BiochemicalEngineering/Biotechnology, Special Issue: Modern Advances inChromatography, Springer, edited by Prof. Dr. R. Freitag.

Biomedical uses of MIPs are described by Liu et al. in “Preparation ofprotein imprinted materials by hierarchical imprinting techniques andapplication in selective depletion of albumin from human serum.” SciRep., 4:5487.doi:10.1038/srep05487, 2014 Jun. 30; by Ciardelli et al. in“The relevance of the transfer of molecular information between naturaland synthetic materials in the realization of biomedical devices withenhanced properties.” J Biomater Sci Polym Ed., 16(2):219-36, 2005; andby Shi. et al. in “Template-imprinted nanostructured surfaces forprotein recognition. Nature, 398(6728):593-7, 1999 Apr. 15.

WO 1995021673 A1 and the publication “Generation of new enzymeinhibitors using imprinted binding sites: the anti-idiotypic approach, astep toward the next generation of molecular imprinting”. J. Am. Chem.Soc., 123(49): 12420-12421, 2001 disclose the use of anti-idiotypicmethods for MIPs.

In molecular imprinting, first a template molecule is selected. Inparticular, biomolecules, for example, vitamins, hormones, or proteinsare used as the template molecule. The template molecule has, dependingon the nature thereof, a plurality of functional groups to whichcomplementary functional groups can bind. Because the functional groupsof the template molecule have a specific arrangement relative to oneanother, the template molecule binds specifically only to anothermolecule that has the complementary arrangement of the complementaryfunctional groups. In nature, signal molecules bind to receptorsaccording to this principle. In molecular imprinting, a receptor for thetemplate molecule is produced artificially, by bringing differentfunctional monomers having different functional groups into contact withthe template molecule, so that the monomers bind to the respectivecomplementary functional group on the template molecule. Doing so doesnot require knowing the arrangement of the functional groups on thetemplate molecule, which plays no role in the process of molecularimprinting. Once bonded to the template molecule, the monomers arecross-linked to one another, such that the monomers are fixed in thepositions and orientations thereof relative to one another, in order toform a polymer. The template molecule is then removed, so that amolecular imprint of the template molecule stays behind in the polymerand can consequently be used as an artificial receptor for the templatemolecule, in particular, a biomolecule. The information content of theimprint or the MIP is limited to whether or not a biomolecule bindsspecifically, i.e., is limited to either a YES or a NO. Molecularlyimprinted polymers (MIPs) can thus be put to use for specificrecognition of the template in chromatographic, extractive, or sensoryapplications.

SUMMARY OF THE INVENTION

This technique has thus far not been used to store data, or to storedigital information or codes.

The invention solves the problem of providing an improved method forstoring values or digital data at the molecular level.

The invention solves this problem in that: in a first step, a templatemolecule or template having a defined sequence of defined functionalgroups is produced, the sequence representing a defined value of anumerical code, preferably, a digital code, or containing digital data;and in a second step, the defined sequence of the template molecule istransferred according to the method of the molecular imprinting to apolymer by bringing the template into contact with monomers that havecomplementary functional groups and therefore align themselves accordingto the sequence of defined functional groups on the template, themonomers being successively fixed to one another by polymerization sothat the functional groups henceforth carry the digital data. Forimproved clarity of reading, the functional groups of the template insuccession are called side functionalities, in order to distinguish theterminology therefor from that for the functional groups of themonomers.

The data carriers according to the invention are thus molecularlyimprinted polymers (MIPs) that contain a defined sequence of monomers ormonomer units having defined functional groups, wherein preferably thefunctional groups of one monomer unit code for 0 and the functionalgroups of another monomer unit code for 1. The information content thuslies in the sequence or order of the functional groups on the MIP, andthus represents a numerical code. The radix (number of differentfunctional groups) of the numerical code is preferably two, such thatthe code is a binary code. If the template is produced with a definedsequence of more than two different functional groups, such thatmonomers or monomer units having more than two different functionalgroups bind to the template, it is also possible to store a numericalcode that has a higher radix than 2 in the MIP according to theinvention.

It is advantageous that selecting the number of monomers and preferablyselecting a suitable cross-linker makes it possible to producemolecularly imprinted polymer data carriers that have differentproperties or shapes, which would not be possible when a molecular datacarrier is produced directly, e.g., as DNA.

Within the scope of the invention, therefore, templates having definedsequences of template molecules, which are available with different sidefunctionalities, are produced first, these sequences being carriers forthe desired numerical code, more particularly, binary code.

The template thus contains a sequence of at least two templatecomponents each having different chemical side functionalities, whereinthese two different side functionalities correspond to the binarynumbers 0 and 1. It may then occur that a template is composed of asequence of only one template component, if, for example, the codeconsists solely of the binary number 0, or solely of the binarynumber 1. In a preferred embodiment, the template is composed of asequence of two template components each having different chemical sidefunctionalities, wherein the sequence contains at least 3, 4, 5, 6, 10,15, 20, or more components.

Examples of possible template components include chemical molecules thatdiffer in the functional side chains thereof, in particular, in the sidefunctionalities thereof. Especially suitable are those molecules thatbear a carboxyl group or primary amino group as a side functionality,preferably as terminal groups. Other functional groups are also suitableas side functionalities, however, provided said functional groups areable to form a connection with a complementary group. As templatecomponents, it is also possible to use: nucleotides; nucleotidederivatives such as, for example, peptide nucleic acids; basic or acidvinyl monomers; oligomerizable anionic or cationic monomer units andother chemically linkable structural units each having additional sidefunctionalities, such as, for example, omega-hydroxycarboxylic acidswith an additional carboxy or amino function, or omega-amino acids withan additional carboxy or amino function.

Examples of especially suitable templates include peptides and proteinsthat are composed of two different amino acids as template components.Preferably, one template component is an acid amino acid, and the othertemplate component is a basic amino acid. The different enantiomers ofthese molecules may then also be used.

Peptide nucleic acid (PNA) structures composed of a sequence of twodifferent nucleobase components are also suitable as templates. Withsuch peptide nucleic acids, the sugar phosphate backbone is replaced,for example, with a pseudopeptide.

With the help of the template or at least one template having a definedsequence of side functionalities, a polymer is imprinted according tothe invention.

The method according to the invention for producing a molecularlyimprinted polymer is performed by imprinting the polymer of themolecularly imprinted polymer by polymerizing the polymer in thepresence of at least one template, wherein the template is composed of adefined, selected sequence of structural components, wherein thestructural components are selected from at least two types of structuralcomponents that differ from one another at least with respect to theside functionalities thereof, wherein templates having any sequence ofthe structural components thereof—i.e., according to any value of thenumerical code—can be produced, wherein at the side functionalities ofthe template, monomers are bonded with the functional groups thereofthat are complementary to the side functionalities, wherein the monomersdiffer from one another with respect to the functional groups thereof,and wherein the monomers are bonded when the polymerization takes placein the polymer structure of the polymer, and the template issubsequently released with the side functionalities thereof from themonomers, so that the molecularly imprinted polymer comprises a definedvalue of the numerical code, more particularly, the binary code, formedof the functional groups of successive monomers, corresponding to theselected sequence of the structural components of the template that wasused to produce the molecularly imprinted polymer.

Preferably, the monomers—more particularly, the functional groupsthereof—are isotopically labelled.

The invention comprises molecularly imprinted polymers (MIPs) containinga defined value of a numerical code, more particularly, a binary code,that are produced according to the method according to the invention.

A preferred embodiment of the invention comprises a molecularlyimprinted polymer (MIP) containing a binary code, wherein themolecularly imprinted polymer (MIP) contains a defined sequence ofmonomers, wherein the functional group of one monomer codes for thebinary number 0 and the functional group of another monomer codes forthe binary number 1.

Another embodiment of the invention comprises a molecularly imprintedpolymer (MIP) containing a numerical code, more particularly, a binarycode, wherein the monomers of the molecularly imprinted polymer (MIP)differ from one another with respect to the functional groups thereof.

Another preferred embodiment of the invention comprises a molecularlyimprinted polymer (MIP) containing a binary code, wherein one monomer ormonomer unit of the MIP has an acidic group, e.g., a carboxyl group, andthe other monomer or other monomer unit of the MIP comprises a basicgroup, e.g., an amino group.

Another preferred embodiment of the invention comprises a molecularlyimprinted polymer (MIP) containing a binary code, wherein one monomer ofthe MIP is methacrylic acid and the other monomer is 2-aminoethylmethacrylate.

Another embodiment of the invention comprises a molecularly imprintedpolymer (MIP) containing a numerical code, more particularly, a binarycode, wherein the sequence of the monomers has at least a length ofthree monomers, wherein the monomers may be identical or different.

A sequence or stored numerical value may preferably have a length of atleast 3, 5, 8, 10, 15, 20, 25, 30, 50 monomers.

Another preferred embodiment of the invention comprises a molecularlyimprinted polymer (MIP) containing a binary code, wherein the sequencehas a length of at least three monomers, wherein at least one monomer ofthe sequence bears a carboxyl group and at least one monomer of thesequence bears an amino function.

Preferably, the molecularly imprinted polymer is produced according tothe following steps:

-   -   a. producing the template, the template being produced as a        freely-definable sequence of template components having        different chemical side functionalities, wherein one template        side functionality can be recognized as logical 1 and one        template side functionality can be recognized as logical 0;    -   b. adding the monomers, which have complementary functional        groups to the side functionalities of the template;    -   c. self-organization by the monomers at the side functionalities        of the template components via the complementary functional        groups thereof;    -   d. fixing the complementary binary code by polymerizing the        monomers in order to produce the polymer; and    -   e. removing the template from the polymer so that the functional        groups of the monomer units are exposed, such that the polymer        exists as a molecularly imprinted polymer, wherein the sequence        of the functional groups forms the defined value of the binary        code.

The complementary monomers, i.e., the monomers added in step b) may beselected, for example, from anionic and cationic monomers. Examples ofanionic monomers include monomers having electron-withdrawingsubstituents, such as nitrile, carboxyl, phenyl, and vinyl groups, suchas acrylic acid, methacrylic acid, crotonic acid, itaconic acid, fumaricacid, maleic acid, monomethyl itaconate, monomethyl fumarate, monobutylfumarate, maleic anhydride, acrylamido glycolic acid, styrenesulfonicacid, vinylsulfonic acid, vinylphosphonic acid,2-acrylamido-2-methylpropane phosphonic acid,2-acrylamido-2-methyl-1-propanesulfonic acid, and derivatives of theanionic monomers mentioned in this paragraph.

Examples of cationic monomers include—but are not limited to—cationicethylenically unsaturated monomers such as diallyldialkylammoniumhalides such as diallyl dimethyl ammonium chloride, the (meth)acrylatesof dialkylaminoalkyl compounds such as dimethylaminoethyl (meth)acrylate, diethylaminoethyl (meth)acrylate, dimethylaminopropyl(meth)acrylate, 2-hydroxydimethylaminopropyl (meth)acrylate, aminoethyl(meth)acrylate, and salts and quaternary compounds thereof,N,N-dialkylaminoalkyl (meth)acrylamide such as N,N-dimethylaminoethylacrylamide and salts and quaternary compounds thereof, and derivativesof the cationic monomers mentioned in this paragraph.

Suitable complementary monomers thus contain complementary functionalgroups.

The molecularly imprinted polymer is preferably biodegradable.

This invention also comprises methods for reading out the code of amolecularly imprinted polymer according to the invention.

A first method according to the invention for reading out the storedinformation of a molecularly imprinted polymer that has a definedsequence of different functional groups reflecting a defined value of anumerical code, more particularly, a binary code, is performed bybringing the molecularly imprinted polymer into contact with a pool ofanalyte templates, wherein the analyte templates have different sidefunctionalities that are complementary to the functional groups of themolecularly imprinted polymer, wherein the analyte templates differ fromone another with respect to the order of side functionalities thereof,so that only that analyte template that has the sequence of sidefunctionalities that is complementary to the functional groups bindsspecifically to a sequence of different functional groups of thenumerical code of the molecularly imprinted polymer.

Thus, that analyte template that corresponds to the template that wasused to produce the molecularly imprinted polymer analyte template bindsspecifically to the molecular imprint of the molecularly imprintedpolymer according to the invention. Preferably, the analyte templates ofthe pool have been isotopically labelled.

A second method according to the invention for reading out the storedinformation of a molecularly imprinted polymer that is selectivelyprovided with a defined sequence of different functional groupsreflecting a defined value of a numerical code, more particularly, abinary code, is performed by using an anti-idiotypic method to read outthe stored information, the method comprising the steps of:

-   -   a. producing a pool of molecules that are template components        having different side functionalities, wherein each type of        template component has one side functionality that is        complementary to one of the functional groups of the defined        sequence;    -   b. bringing the pool of template components into contact with        the molecularly imprinted polymer, wherein the imprint of the        molecularly imprinted polymer that has the stored value of the        numerical code acts as a reaction chamber, so that template        components bind to the different functional groups of the        imprint according to the respective side functionalities        thereof, such that a replica of the template that may have been        used or was used to produce the stored value of the numerical        code is created in the imprint; and    -   c. reading out the stored value by characterization of replicas        by means of an analytical method.

The second method according to the invention for reading out the valueof the code of the MIP thus differs from the first in that only thetemplate components are used, instead of templates composed of bondedtemplate components. This is advantageous in that it is not necessary toproduce all of the relevant variants of analyte templates and bring thesame into contact with the molecularly imprinted polymer, but ratheronly the template components from which the templates or analytetemplates were formed. In the case of a binary code, thus, only twodifferent template components are required in the second readout methodaccording to the invention.

Preferably, the template components of the pool have been isotopicallylabelled.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings provide a more detailed illustration, by way of example, ofthe method according to the invention on the basis of several embodimentvariants. The drawings show:

FIG. 1. an exemplary template molecule having a binary code based on twodifferent template components (lysine and glutamic acid);

FIG. 2. an exemplary template molecule in electrostatic interaction withcorresponding, complementary functional monomers;

FIG. 3. the molecular imprint of the exemplary template molecule in thepolymer, wherein the template molecule is still embedded;

FIG. 4. the molecular imprint of the exemplary template molecule in thepolymer, after the template molecule has been removed;

FIG. 5. the specific recognition of the binary code stored in themolecular imprint of the polymer, through the template molecule; and

FIG. 6. the reading out of the stored binary code throughspatially-resolved solid state NMR in the molecular imprint. Selectiveisotopic labelling of the molecular imprint or the monomer units andtemplate molecules enables magnetic dipolar interactions.

In the chemical structural formula, “PG” stands for “protecting group.”

DETAILED DESCRIPTION

The octapeptide lysine-lysine-lysine-lysine-lysine-glutamicacid-glutamic acid-lysine is used as a template 1, by way of example(see FIG. 1). With lysine and glutamic acid, the template 1 has twodifferent template components that differ from one another with respectto the side functionalities 2, 3 thereof. In the example of FIG. 1, theamino function, as the side functionality 2 of the lysine, acts as abinary “1” while the carboxyl function, as the side functionality 3 ofthe glutamic acid, acts as a binary “0.” The following sequence of sidefunctionalities 2, 3—read from left to right—thus arises for the exampletemplate 1 depicted in FIG. 1:Amino-Amino-Amino-Amino-Amino-Carboxy-Carboxy-Amino, thus 11111001 asthe value of the binary code 4.

The addition of at least two different monomers 5 having functionalgroups 6, 7 that are complementary to the side functionalities 2, 3 ofthe template 1 is followed then by a wait for the self-organization ofthe template 1 and monomers 5 via the functionalities thereof, so thatthe monomers 5 bind to the side functionalities 2, 3 according to thefunctional groups 6, 7 thereof, as is illustrated in FIG. 2.

Suitable monomers 5 thus contain complementary functional groups. Thus,as illustrated in the example, the first monomer 5—methacrylic acid,with the functional group 6 thereof—is complementary to the sidefunctionality 2 in the form of the amino function of the templatecomponent lysine. The second monomer 5, in the form of 2-aminoethylmethacrylate with the functional group 7 thereof in the form of anamino-functionalized side chain, is complementary to the sidefunctionality 3 in the form of the carboxy function of the templatecomponent glutamic acid. Thus, the functionally complementary monomers 5organize themselves with the template components through thecomplementary functional groups thereof. In the example of FIG. 2, theacid function of the methacrylic acid organizes itself with the basicfunction of the lysine, and the basic function of the 2-aminoethylmethacrylate organizes itself with the acidic function of the glutamicacid of the octapeptide that forms the template 1. Electrostaticinteractions thus form stable compounds.

After a cross-linking monomer has been added, the monomers 5 can bepolymerized to thereby fix and store the complementary templatestructure and thus the binary code 4. Examples of suitable monomericcross-linkers include ethylene glycol dimethacrylate, butylene glycoldimethacrylate (or butane-1,4-diol dimethacrylate), and hexamethylenedimethacrylate (or hexane-1,6-diol dimethacrylate).

In FIG. 3, the monomers 5 are depicted in the cross-linked statethereof, i.e., the monomers are components of a polymer 8 or are bondedto a polymer 8. As is represented, the template 1 is still bonded to thepolymer 8 after the polymerization.

As depicted in FIG. 4, the template 1 is removed from the polymer 8.After the template 1 has been removed with the original binary code 4thereof, then, the functionalities of the previous monomers 5 remainbehind in the resulting molecular imprints of the polymer 8 in animmobilized configuration, such as the template 1 was set forth. Thepolymer 8, after the template 1 has been removed, thus exists as themolecularly imprinted polymer 9. The molecularly imprinted polymer 9has, in an exposed state, the functional groups 6, 7 of the cross-linkedmonomers 5, which form the binary code 4 of the molecularly imprintedpolymer 9, i.e., according to the example, the code sequence or thestored value 11111001.

As illustrated in FIG. 5, the thus-stored value of the binary code 4 isread out from the molecular imprints of the MIPs 9 according to a firstvariant according to the invention by stirring a mixture of analytetemplates 10 also containing an analyte template 10 that corresponds tothe original template 1 with a suspension of MIP particles, andmeasuring the residual content of the analyte templates 10 in thesupernatant of the MIP particles after an adsorption phase. The contentof the analyte template 10 that corresponds to the original template 1is diminished in comparison to the other analyte template 10 becausethat analyte template 10 binds specifically as the sole molecule in themolecular imprints. This makes it possible to determine which value ofthe binary code 4 is present in the molecular imprint of the MIP 9. Asshown, the analyte template 10 that has the sequence of sidefunctionalities 2, 3 that is complementary to the sequence of thefunctional groups 6, 7 of the MIP 9 binds specifically to the imprint,i.e., the sequence 22222332 binds specifically to the sequence 66666776,i.e., according to the example, the side functionality sequenceAmino-Amino-Amino-Amino-Amino-Carboxy-Carboxy-Amino of the templatecomponent sequence Lysine-Lysine-Lysine-Lysine-Lysine-Glutamicacid-Glutamic acid-Lysine binds to the functional group sequenceCarboxy-Carboxy-Carboxy-Carboxy-Carboxy-Amino-Amino-Carboxy of themonomers 5.

According to a second readout method according to the invention, thebinary code 4 may also be read out by adding solutions of chemicalstructural components of the original template molecules according to atype of anti-idiotypic method and then replicating these templatemolecules in the molecular imprints, it being possible to determine thecode thereof after elution and analytical characterization. This secondreadout method according to the invention is thus performed by producinga pool of molecules that contain at least the original templatecomponents of the template 1 that was used to produce the MIP 9. Thispool is brought into contact with the MIP 9, wherein the molecularimprint, i.e., the binary code 4, of the MIP 9 acts as a reactionchamber. The complementary template components of the pool bind to themolecular imprint, thereby producing replicas of the original templates1. These replicas may be characterized by means of analytical methods,for example, by means of chromatographic methods, and thus the storedcode 4 can be read out. The molecular imprint in the MIP 9 may act, onthe one hand, as a copy room for replicating the original template 1,while the molecular imprint may also be used, on the other hand, toproduce different variants or derivatives of the original template 1,depending on the choice of chemical components, with an unalteredsequence of the side group functionalities, i.e., of the binary code 4.In other words, the code in the MIP 9 can be used to produce duplicatesor derivatives of the template 1, which can be used in turn as data orinformation carriers, or can be used to produce other MIPs 9. The MIPs 9according to the invention can thus be copied or replicated.

FIG. 6 illustrates a method for reading out the stored binary codedirectly at the MIP 9 by spatially-resolving solid state NMR. NMR standsfor nuclear magnetic resonance. It is to be provided according to theinvention that the monomers 5 and the template component binding theretohave a selective isotopic labelling, which is achieved, for example, byselecting the nitrogen atoms of the amino functions and the carbon atomsof the carboxy functions of both the side functionalities 2, 3 of thetemplate components and the functional groups 6, 7 of the monomers 5 inthe form of ¹⁵N and ¹³C isotopes, respectively. Withspatially-resolving, multi-nuclear, multi-dimensional solid state NMR,the binary code 4 is read out according to the invention by measuring adipolar recoupling by means of rotational echo double resonance (REDOR)or radio frequency-driven recoupling (RFDR) spectroscopy on the basis ofthe aforementioned isotopic labelling, and thus being able to determinethe structure and orientation of the template 1, or an identical analytetemplate 10, in the MIP 9 and thus the order of the functional groups 6,7 in the MIP 9 and therewith the value of the binary code 4.

The isotopically labelled template components in the MIP 9 may, on thebasis of the first readout method according to the invention, be bondedby bringing a pool of different isotopically labelled analyte templates10 differing from one another in the order of the isotopically labelledtemplate components thereof in contact with the MIP 9, so that only thatisotopically labelled analyte template 10 that has the value of thebinary code 4 of the original template 1 binds to the imprint of the MIP9, as is illustrated in FIG. 6.

The second readout method according to the invention—which follows atype of anti-idiotypic method—may preferably be carried out withisotopically labelled template components. The isotopically labelledtemplate components bind with the respective side functionalities 2, 3thereof to the complementary functional groups 6, 7 of the imprint,i.e., according to the order of the binary code 4, such that theisotopically labelled template components together form a duplicate orderivative of the original template 1, which exists according to theanalyte template 10 of FIG. 6 in the isotopically labelled imprint ofthe MIP 9.

Because the measurable interaction between the isotopes of the bondedanalyte template 10 and the isotopes of the monomers 5 differ accordingto the order of the arrangements thereof, the value of the binary code 4can be determined directly at the MIP 9.

The molecularly imprinted polymers 9 described herein are produced inthe presence of the template 1, preferably via a surface, precipitation,suspension, emulsion, or mass polymerization in a batch or semi-batchprocess, and put to use in different forms, preferably in the form ofspherical particles, or—especially preferably—in the form of polymercoatings.

The spherical particles or polymer coatings may be used, for example, toencode for products of every kind. Due to the size down to the nanometerrange, the MIPs 9 are invisible to the consumer when applied tolong-lasting products, so that the origin thereof can be unambiguouslydetermined even after a long period of time has passed. The MIPs 9 canthus contain, for example, detailed information on the actual origin ofthe original products, so that the products can be distinguished fromcounterfeits. Plastic matrices may be provided directly with thedescribed molecular imprints and thus be encoded or generally put to useas data carriers. For example, specific manufacturer or customer data,or simply the date of production, may be left as a numerical value or inbinary form in the imprint.

It is also possible to produce multi-MIPs 9, wherein a plurality ofdifferent templates 1 are used, in order to imprint, in parallel,different numerical codes, more particularly, binary codes 4 havingdifferent information into molecular imprints. One MIP 9 can thuscomprise a plurality of different molecular imprints, which may differfrom one another with respect to the code sequence and/or code lengththereof.

Thus, another embodiment comprises MIPs 9 that contain at least twodifferent values of a numerical code, more particularly, a binary code4.

In one embodiment of the invention, the MIPs 9 are used to recognizeand/or code for foodstuffs, consumer goods, industrial goods, andcomponents or ingredients thereof.

Example 1

To produce a molecularly imprinted polymer 9 according to the inventionas an example, the tripeptide glutamic acid-lysin-lysine (EKK) was usedas the template 1. The value of the binary code 4 present in the aminoacid sequence corresponds thus to 100. The formulation of this templatepolymer is set forth in table 1.

TABLE 1 Composition of the molecularly imprinted polymer (MIP1) with useof the template EKK, with molar mass, calculated and actually- measuredmass of the substances, and the equivalents thereof Molar mass Substanceg/mol Estimated Actual Equivalent Template EKK 625.31 15 mg 15.67 mg 1Methacrylamide 86.04 33.00 mg 33.54 mg 15.6 Methacrylic acid 85.05 32.64mg 33.65 mg 15.8 Ethylene glycol 198.22 237.75 mg 237.38 mg 47.8dimethacrylate Azobisisobutyro- 164.21 1.17 mg 1.42 mg 0.35 nitrileAcetonitrile 41.05 3.75 mL 3.75 mL — Di- 78.13 — 0.2 mL —methylsulfoxide

With the exception of the initiator azobisisobutyronitrile, all of thecomponents were dissolved in a mixture of acetonitrile and dimethylsulfoxide. The solution was stirred for 4 hours in order to make itpossible to create electrostatic interactions such as hydrogen bondsand—in addition, after proton transfer—ionic bonds between the template1 and the functional monomers 5 methacrylamide and methacrylic acid. Theinitiator azobisisobutyronitrile is then added thereto, and the solutionwas sprayed for 5 minutes with gaseous nitrogen. Then, in a refrigeratorat 6° C., the solution was placed in a UV reactor and subjected to 24hours of UV radiation. The suspension formed was subsequently stirredfor 24 hours with 6 mL of a methanol-acetic acid mixture (9:1, v:v), inorder to purify the polymer 8 and, in particular, to remove the templatemolecules. The resulting molecularly imprinted polymer 9 was thenfiltered and washed twice with a methanol-acetic acid mixture and fourtimes with acetonitrile. The molecularly imprinted polymer 9 wassubjected to 5 more minutes of suction as a first round of drying.Further drying steps included spraying the solid with gaseous nitrogenfor 5 minutes, and depositing in a drying oven at 40° C. for a period of24 hours. The yield of the white-colored, powdery molecularly imprintedpolymer 9 was 219.66 mg.

The template 1 (the tripeptide EKK) as analyte and other comparisonanalytes/analyte templates 10 (the tripeptides KEK, EKE, EEK, EEE) wereeach dissolved in 0.1 mL of dimethyl sulfoxide and 8 mL of acetonitrile,and the powdery MIP 9 was suspended therein. Table 2 lists the exactdetails of these affinity assays. These suspensions were each stirredfor 18 hours at room temperature. 2 mL was then removed from each ofthese suspensions and centrifuged at a rotational speed of 10,000 RPM.The resulting supernatants were diluted with 8 mL of acetonitrile andthe solutions were then subjected to spectroscopic measurement at awavelength of 300 nm.

TABLE 2 Affinity assays with the molecularly imprinted polymer MIP1 withdifferent tripeptides, the absolute masses used thereof, the masses ofthe molecularly imprinted polymer MIP1 used, and the measuredconcentrations of the tripeptides in the supernatant after reachingequilibrium. Concentration in Analyte supernatant based on (peptide Massmeasured absorption sequence) of analyte/mg Mass of MIP/mg C_(calc),mg/mL KEK 2.11 10.43 0.073 EKK* 2.12 10.39 0.043 EKE 2.08 10.20 0.069EEK 2.10 9.94 0.072 EEE 2.16 10.31 0.117 (E = glutamic acid, K =lysine) * corresponds to the original template molecule

This example showed that the MIP 1 has a particular affinity to theoriginal template EKK (line marked with *), with an especially highadsorption due to specific molecular imprints, or with an especially lowresidual content in the supernatant of only 0.043 mg/mL, in comparisonto the four other tripeptides KEK (0.073 mg/mL), EKE (0.069 mg/mL), EEK(0.072 mg/mL), and EEE (0.117 mg/mL). In this manner, it was possible toread back, from a key set of five tripeptide molecules (KEK, EKK, EKE,EEK, and EEE), the matching key (EKK) due to the stored information,i.e., the sequence EKK or the binary code 100.

The invention claimed is:
 1. A method for producing a molecularly imprinted polymer containing at least one defined value of a numerical code, comprising: storing the value of the numerical code in the polymer of the molecularly imprinted polymer by polymerizing the polymer in the presence of at least one template, the template being composed of a defined, selected sequence of structural components, the structural components being selected from at least two types of structural components that differ from one another at least with respect to side functionalities thereof; wherein templates having any sequence of the structural components thereof can be produced; wherein monomers comprising functional groups are bonded by said functional groups to complementary side functionalities of the template; wherein at least two types of monomers are used that differ from one another with respect to said functional groups thereof; and wherein, when polymerizing the polymer, said monomers are bonded in a polymer structure of the polymer, and the template is subsequently released by said side functionalities of said template releasing said functional groups of said monomers, so that the molecularly imprinted polymer comprises a defined value of the numerical code, formed by said functional groups of successive monomers, corresponding to the defined, selected sequence of said structural components of said template that was used to produce the molecularly imprinted polymer.
 2. The method according to claim 1, wherein: two different types of template components and two different monomers are present; and the first monomer has an acidic group as said functional group and the second monomer has a basic group as said functional group.
 3. The method according to claim 2, wherein the first monomer has a carboxyl group as said functional group and the second monomer has an amino group as said functional group.
 4. The method according to claim 1, wherein the monomers are selected from the group consisting of: acrylic acid; methacrylic acid; crotonic acid; itaconic acid; fumaric acid; maleic acid; monomethyl itaconate; monomethyl fumarate; monobutyl fumarate; maleic anhydride; acrylamido glycolic acid; styrenesulfonic acid; vinylsulfonic acid; vinylphosphonic acid; 2-acrylamido-2-methylpropanephosphonic acid; 2-acrylamido-2-methyl-1-propanesulfonic acid; diallyl dimethyl ammonium chloride; dimethylaminoethyl (meth)acrylate; diethylaminoethyl (meth)acrylate; dimethylaminopropyl (meth)acrylate; 2-hydroxydimethylaminopropyl (meth)acrylate; aminoethyl (meth)acrylate and salts and quaternary compounds thereof; N,N-dimethylaminoethyl acrylamide; as well as derivatives of said monomers.
 5. The method according to claim 1, wherein: the defined value of the numerical code is formed of at least three monomers; and a sequence of the numerical code from monomers may be composed of identical monomers, or of different monomers.
 6. The method according to claim 1, wherein the polymerizing is carried out in the presence of at least two different templates that differ from one another with respect to a sequence of the side functionalities bonded thereto, so that the molecularly imprinted polymer contains at least two different defined values of a numerical code.
 7. The method according to claim 1 for producing a molecularly imprinted polymer containing a defined value of a binary code, the method comprising the steps of: a. producing the template, the template being produced as a freely-definable sequence of template components having different chemical side functionalities, wherein one template side functionality can be recognized as logical 1 and one template side functionality can be recognized as logical 0; b. adding the monomers, which have complementary functional groups to the side functionalities of the template; c. self-organizing of the monomers at the side functionalities of the template components via the complementary functional groups thereof; d. fixing said binary code by polymerizing the monomers in order to produce the polymer; and e. removing the template from the polymer so that the functional groups of the monomers are exposed, such that the polymer exists as a molecularly imprinted polymer, wherein the sequence of the functional groups forms the defined value of said binary code.
 8. The method according to claim 1, wherein a first side functionality of the template is a carboxyl group and a second side functionality of the template is a primary amino group.
 9. The method according to claim 1, wherein: the template comprises a sequence of at least three template components; and the group of templates from which the template can be selected also includes templates that have only template components having one type of side functionality.
 10. The method according to claim 1, wherein the template components are selected from the group consisting of: basic or acidic amino acids; nucleotides; nucleotide derivatives; basic or acidic vinyl monomers; anionic or cationic monomer units; chemically cross-linkable structural units having omega-hydroxycarboxylic acids and an additional carboxy or amino function; and omega-amino acids having a carboxy or amino function.
 11. The method according to claim 1, wherein the monomers are polymerized with the use of a cross-linker.
 12. A molecularly imprinted polymer containing a molecularly stored value of a numerical code, wherein the molecularly imprinted polymer—and, thus, also the molecularly stored value—has been produced according to the method according to claim
 1. 13. The molecularly imprinted polymer according to claim 12, wherein the molecularly imprinted polymer is a food, a consumer good, or an industrial good, or a component and/or ingredient thereof, wherein the molecularly stored value makes it possible to identify the food, the consumer goods, or industrial goods, or contains information regarding the same.
 14. Use of the molecularly imprinted polymer according to claim 12 to label, code for, and/or analyze products.
 15. Use of the molecularly imprinted polymer according to claim 14 to recognize and/or code for food, consumer goods, or industrial goods and/or components or ingredients thereof.
 16. A method for producing a molecularly imprinted polymer containing at least one defined value of a numerical code, the method employing: at least one template, the template being composed of a defined, selected sequence of structural components, the structural components being selected from at least two types of structural components that differ from one another at least with respect to side functionalities thereof, wherein templates having any sequence of the structural components thereof can be produced; and multiple monomers each comprising a functional group; wherein at least two types of monomers are used that differ from one another with respect to said functional group thereof; wherein the method comprises: bringing said monomers in contact with at least one template such that monomers bond with their functional groups to complementary side functionalities of said template, such that said functional groups of successive monomers, are arranged in a sequence that is complementary to said defined, selected sequence of said template used; polymerizing said monomers such that they are bonded in a polymer structure of a polymer; and releasing said template from said polymer by releasing said side functionalities of said template from said functional groups of said monomers, resulting in said molecularly imprinted polymer that comprises said defined value of said numerical code, which defined value is formed by said sequence of said functional groups.
 17. The method according to claim 16, wherein, of said monomers a first type of monomers has an acidic group as said functional group and a second type of monomers has a basic group as said functional group.
 18. The method according to claim 16, wherein, of said side functionalities a side functionality of a first type of structural component is a carboxyl group and a side functionality of a second type of structural component is a primary amino group.
 19. The method according to claim 16, wherein: the numerical code is a binary code; and the method further comprises producing the template, the template being produced as a freely-definable sequence of template components having different chemical side functionalities, wherein one template side functionality can be recognized as a logical 1 and one template side functionality can be recognized as a logical
 0. 20. A method for producing a molecularly imprinted polymer including a defined numerical code, the method comprising: bonding a plurality of monomers to a template, the plurality of monomers comprising functional groups, the plurality of monomers comprising at least a first monomer including a first functional group of the functional groups and a second monomer including a second functional group of the functional groups, the template comprising a defined sequence of structural components, the structural components comprising side functionalities, the structural components comprising at least a first structural component including a first side functionality of the structural components and a second structural component including a second side functionality of the structural components, the first functional group bonding with the first side functionality and the second functional group bonding with the second side functionality such that the functional groups of the plurality of monomers bonded to the template are arranged in a sequence complementary to the defined sequence of the structural components; polymerizing the plurality of monomers to form one polymer; and detaching the template from the polymer by releasing the side functionalities from the functional groups to form the molecularly imprinted polymer, the molecularly imprinted polymer comprising the defined numerical code by the sequence of the functional groups.
 21. The method according to claim 20, wherein said first monomer has an acidic group as said first functional group and said second monomer has a basic group as said second functional group.
 22. The method according to claim 20, wherein said first side functionality of said first structural component is a carboxyl group and said second side functionality of said second structural component is a primary amino group. 